Skip to main content
SpringerLink
Log in

Synthesis of Biocompatible Chitosan Nanoparticles by Some Greener Methods for Drug Encapsulations

  • Reference work entry
  • First Online:
Handbook of Consumer Nanoproducts

Abstract

Chitosan is obtained from chitin, and it is the second most abundant biopolymer after cellulose. Chitosan is biocompatible and biodegradable, hence an ideal biomaterial for drug encapsulation and delivery. But chitosan is not soluble in water which is a major bottleneck of chitosan for its biomedical applications. In this chapter, we have discussed some greener methods of making water-soluble chitosan nanoparticles and their drug-encapsulating behaviors. Basically, this chapter describes depolymerization of water-insoluble larger chitosan polymers followed by formation of compact nanostructure by cross-linking. Discussions on different types of cross-linking agent and nature of cross-linked chitosan nanoparticles have been presented. Recent reports on drug encapsulation by chitosan nanoparticles, their stability at different pH, and their biomedical applications have been highlighted. Methods of encapsulation of different types of drugs (hydrophilic or hydrophobic) within the chitosan particles have been cited.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 699.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 799.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Hussain CM (2018) Handbook of nanomaterials for industrial applications. Elsevier

    Google Scholar 

  2. Hussain CM, Mishra AK (2019) Nanotechnology in environmental Science, 2 vols. Wiley

    Google Scholar 

  3. Hussain CM (2020) The ELSI handbook of nanotechnology: risk, safety, ELSI and commercialization. Wiley

    Book  Google Scholar 

  4. Hussain CM (2020) Handbook of functionalized nanomaterials for industrial applications. Elsevier

    Google Scholar 

  5. Hussain CM (2020) Handbook of manufacturing applications of nanomaterials. Elsevier

    Google Scholar 

  6. Hussain CM (2020) Handbook of polymer Nanocomposites for industrial applications. Elsevier

    Google Scholar 

  7. Yang J, Han S, Zheng H, Hongbiao D, Liu J (2015) Preparation and application of micro/nanoparticles based on natural polysaccharides. Carbohydr Polym 123

    Google Scholar 

  8. Ravi Kumar MNV (2000) A review of chitin and chitosan applications. React Funct Polym 46:1–27

    Article  Google Scholar 

  9. Bhattarai N, Gunn J, Zhang M (2010) Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliv Rev 62:83–99

    Article  CAS  Google Scholar 

  10. Basumallick S, Campos MGN, Richardson D, Gesquiere A, Santra S (2016) Hydrothermally treated chitosan spontaneously forms water-soluble spherical particles stable at a wide pH range. Int J Polym Mater Polym Biomater 65:751–758

    Article  CAS  Google Scholar 

  11. Nasti A, Zaki NM, de Leonardis P, Ungphaiboon S, Sansongsak P, Rimoli MG, Tirelli N (2009) Chitosan/TPP and chitosan/TPP-hyaluronic acid nanoparticles: systematic optimisation of the preparative process and preliminary biological evaluation. Pharm Res 26:1918–1930

    Article  CAS  Google Scholar 

  12. Janes K, Alonso M (2003) Depolymerized chitosan nanoparticles for protein delivery: preparation and characterization. J Appl Polym Sci 88:2769–2776

    Article  CAS  Google Scholar 

  13. Cui Z, Mumper RJ (2001) Chitosan-based nanoparticles for topical genetic immunization. J Control Release 75:409–419

    Article  CAS  Google Scholar 

  14. Banerjee T, Mitra S, Singh A, Sharma R, Maitra A (2002) Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles. Int J Pharm 243:93–105

    Article  CAS  Google Scholar 

  15. Liu C-G, Desai KGH, Chen X-G, Park H-J (2005) Preparation and characterization of nanoparticles containing trypsin based on hydrophobically modified chitosan. J Agric Food Chem 53:1728–1733

    Article  CAS  Google Scholar 

  16. Basumallick S (2019) Alginates: applications in the biomedical and food industries. Wiley

    Google Scholar 

  17. Brunel F, Véron L, David L, Domard A, Delair T (2008) A novel synthesis of chitosan nanoparticles in reverse emulsion. Langmuir 24:11370–11377

    Article  CAS  Google Scholar 

  18. Kafshgari M, Khorram M, Mansouri M, Samimi A, Osfouri S (2012) Preparation of alginate and chitosan nanoparticles using a new reverse micellar system. Iran Polym J 21

    Google Scholar 

  19. Seidi F, Heshmati P, Galehdari S, Tajehmiri A, Salimi H (2016) Synthesis of water soluble quaternary chitosan derivative via protection-deprotection strategy and investigation of its antibacterial effect. Polym Sci Ser B 58:341–346

    Article  CAS  Google Scholar 

  20. Bukzem AL, Signini R, dos Santos DM, Lião LM, Ascheri DPR (2016) Optimization of carboxymethyl chitosan synthesis using response surface methodology and desirability function. Int J Biol Macromol 85:615–624

    Article  CAS  Google Scholar 

  21. Baran T, Menteş A (2015) Cu(II) and Pd(II) complexes of water soluble O-carboxymethyl chitosan Schiff bases: synthesis, characterization. Int J Biol Macromol 79:542–554

    Article  CAS  Google Scholar 

  22. Mivehi L, Hajir Bahrami S, Malek RMA (2008) Properties of polyacrylonitrile-N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride blend films and fibers. J Appl Polym Sci 109:545–554

    Article  CAS  Google Scholar 

  23. Zhang J, Tan W, Zhang Z, Song Y, Li Q, Dong F, Guo Z (2018) Synthesis, characterization, and the antifungal activity of chitosan derivatives containing urea groups. Int J Biol Macromol 109:1061–1067

    Article  CAS  Google Scholar 

  24. Khalil ES, Saad B, Negim E-SM, Saleh MI (2015) Novel water-soluble chitosan derivative prepared by graft polymerization of dicyandiamide: synthesis, characterisation, and its antibacterial property. J Polym Res 22:116

    Article  CAS  Google Scholar 

  25. Chang C-T, Lin Y-L, Lu S-W, Huang C-W, Wang Y-T, Chung Y-C (2016) Characterization of a Chitosanase from jelly fig (Ficus awkeotsang Makino) latex and its application in the production of water-soluble low molecular weight Chitosans. PLoS One 11:e0150490–e0150490

    Article  CAS  Google Scholar 

  26. Xiao B, Wan Y, Wang X, Zha Q, Liu H, Qiu Z, Zhang S (2011) Synthesis and characterization of N-(2-hydroxy)propyl-3-trimethyl ammonium chitosan chloride for potential application in gene delivery. Colloid Surf B Biointerf 91:168–174

    Article  CAS  Google Scholar 

  27. Tao W, Zheng H-Q, Fu T, He Z-J, Hong Y (2017) N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride: an immune-enhancing adjuvant for hepatitis E virus recombinant polypeptide vaccine in mice. Hum Vaccin Immunother 13:1818–1822

    Article  Google Scholar 

  28. Lin FJ, Lin F, Jia HR, Wu FG (2019) Glycol chitosan: a water-soluble polymer for cell imaging and drug delivery. Molecules 24:4371

    Article  CAS  Google Scholar 

  29. Xiao C, Sun F (2013) Fabrication of distilled water-soluble chitosan/alginate functional multilayer composite microspheres. Carbohydr Polym 98:1366–1370

    Article  CAS  Google Scholar 

  30. Lacerda L, Parize AL, Fávere V, Laranjeira MCM, Stulzer HK (2014) Development and evaluation of pH-sensitive sodium alginate/chitosan microparticles containing the antituberculosis drug rifampicin. Mater Sci Eng C 39:161–167

    Article  CAS  Google Scholar 

  31. Aziz MA, Cabral JD, Brooks HJL, Moratti SC, Hanton LR (2012) Antimicrobial properties of a chitosan dextran-based hydrogel for surgical use. Antimicrob Agents Chemother 56:280–287

    Article  CAS  Google Scholar 

  32. Hong DY, Lee J-S, Lee HG (2016) Chitosan/poly-γ-glutamic acid nanoparticles improve the solubility of lutein. Int J Biol Macromol 85:9–15

    Article  CAS  Google Scholar 

  33. Oyarzun-Ampuero FA, Brea J, Loza MI, Torres D, Alonso MJ (2009) Chitosan-hyaluronic acid nanoparticles loaded with heparin for the treatment of asthma. Int J Pharm 381:122–129

    Article  CAS  Google Scholar 

  34. Wang M-J, Xie Y-L, Zheng Q-D, Yao S-J (2009) A novel, potential microflora-activated carrier for a colon-specific drug delivery system and its characteristics. Ind Eng Chem Res 48:5276–5284

    Article  CAS  Google Scholar 

  35. Wu Q-X, Lin D-Q, Yao S-J (2014) Design of chitosan and its water soluble derivatives-based drug carriers with polyelectrolyte complexes. Mar Drugs 12:6236–6253

    Article  CAS  Google Scholar 

  36. Aguirre-Loredo RY, Rodríguez-Hernández AI, Chavarría-Hernández N (2014) Physical properties of emulsified films based on chitosan and oleic acid. CyTA J Food 12:305–312

    Article  CAS  Google Scholar 

  37. Katugampola P, Winstead C (2014) Rheological behavior and thermal stability of palmitoyl chitosan varying the degree of substitution

    Google Scholar 

  38. Belamie E, Domard A, GiraudGuille MM (1997) Study of the solid-state hydrolysis of chitosan in presence of HCl. J Polym Sci Part a-Polym Chem 35:3181–3191

    Article  CAS  Google Scholar 

  39. Jia ZS, Shen DF (2002) Effect of reaction temperature and reaction time on the preparation of low-molecular-weight chitosan using phosphoric acid. Carbohydr Polym 49:393–396

    Article  CAS  Google Scholar 

  40. Zamani A, Taherzadeh MJ (2010) Production of low molecular weight chitosan by hot dilute SULFURIC acid. Bioresources 5:1554–1564

    CAS  Google Scholar 

  41. Chen RH, Chen WY, Wang ST, Hsu CH, Tsai ML (2009) Changes in the mark-Houwink hydrodynamic volume of chitosan molecules in solutions of different organic acids, at different temperatures and ionic strengths. Carbohydr Polym 78:902–907

    Article  CAS  Google Scholar 

  42. Chang KLB, Tai MC, Cheng FH (2001) Kinetics and products of the degradation of chitosan by hydrogen peroxide. J Agric Food Chem 49:4845–4851

    Article  CAS  Google Scholar 

  43. Seo S, King JM, Prinyawiwatkul W (2007) Simultaneous depolymerization and decolorization of chitosan by ozone treatment. J Food Sci 72:C522–C526

    Article  CAS  Google Scholar 

  44. Hsu SC, Don TM, Chiu WY (2002) Free radical degradation of chitosan with potassium persulfate. Polym Degrad Stab 75:73–83

    Article  CAS  Google Scholar 

  45. Shen K, Hu Q, Wang Z, Qu J (2011) Effect of co-60 irradiation on the properties of chitosan rod. Mater Sci Eng C-Mater Biol Appl 31:866–872

    Article  CAS  Google Scholar 

  46. Tahtat D, Mahlous M, Benamer S, Khodja AN, Youcef SL (2012) Effect of molecular weight on radiation chemical degradation yield of chain scission of gamma-irradiated chitosan in solid state and in aqueous solution. Radiat Phys Chem 81:659–665

    Article  CAS  Google Scholar 

  47. Cravotto G, Tagliapietra S, Robaldo B, Trotta M (2005) Chemical modification of chitosan under high-intensity ultrasound. Ultrason Sonochem 12:95–98

    Article  CAS  Google Scholar 

  48. Czechowska-Biskup R, Rokita B, Lotfy S, Ulanski P, Rosiak JM (2005) Degradation of chitosan and starch by 360-kHz ultrasound. Carbohydr Polym 60:175–184

    Article  CAS  Google Scholar 

  49. Demin VA, Kabalnova NN, Osipova GI, Shereshovetz VV (1993) Depolymerization of cellulose upon ozonation. Russ J Appl Chem 66:2562

    CAS  Google Scholar 

  50. Kabal'nova NN, Murinov KY, Mullagaliev IR, Krasnogorskaya NN, Shereshovets VV, Monakov YB, Zaikov GE Oxidative destruction of chitosan under the effect of ozone and hydrogen peroxide, in, 2001

    Google Scholar 

  51. Liu Yanru CS, Ping Y (1997) The preparation of water soluble low molecular weight chitosan and the complex with calcium ions. J Fujian Teachers Univ Nat Sci 3

    Google Scholar 

  52. Tian F, Liu Y, Hu KA, Zhao BY (2004) Study of the depolymerization behavior of chitosan by hydrogen peroxide. Carbohydr Polym 57:31–37

    Article  CAS  Google Scholar 

  53. Allan GG, Peyron M (1995) Molecular-weight manipulation of chitosan .1. Kinetics of depolymerization by nitrous-acid. Carbohydr Res 277:257–272

    Article  CAS  Google Scholar 

  54. Allan GG, Peyron M (1995) Molecular-weight manipulation of chitosan .2. Prediction and control of extent of depolymerization by nitrous-acid. Carbohydr Res 277:273–282

    Article  CAS  Google Scholar 

  55. Azevedo EP, Mariappan SVS, Kumar V (2012) Preparation and characterization of chitosans carrying aldehyde functions generated by nitrogen oxides. Carbohydr Polym 87:1925–1932

    Article  CAS  Google Scholar 

  56. Tsao CT, Chang CH, Lin YY, Wu MF, Han JL, Hsieh KH (2011) Kinetic study of acid depolymerization of chitosan and effects of low molecular weight chitosan on erythrocyte rouleaux formation. Carbohydr Res 346:94–102

    Article  CAS  Google Scholar 

  57. Zhang Z, Li C, Wang Q, Zhao ZK (2009) Efficient hydrolysis of chitosan in ionic liquids. Carbohydr Polym 78:685–689

    Article  CAS  Google Scholar 

  58. Huang QZ, Zhuo LH, Guo YC (2008) Heterogeneous degradation of chitosan with H2O2 catalysed by phosphotungstate. Carbohydr Polym 72:500–505

    Article  CAS  Google Scholar 

  59. Sato K, Saimoto H, Morimoto M, Shigemasa Y (2003) Depolymerization of chitin and chitosan under hydrothermal conditions. Sen'i Gakkaishi 59:104–109

    Article  CAS  Google Scholar 

  60. Kaushik AY, Tiwari AK, Gaur A (2015) Role of excipients and polymeric advancements in preparation of floating drug delivery systems. Int J Pharm Investig 5:1–12

    Article  CAS  Google Scholar 

  61. Lee S-T, Mi F-L, Shen Y-J, Shyu S-S (2001) Equilibrium and kinetic studies of copper(II) ion uptake by chitosan-tripolyphosphate chelating resin. Polymer 42:1879–1892

    Article  CAS  Google Scholar 

  62. de Pinho Neves AL, Milioli CC, Müller L, Riella HG, Kuhnen NC, Stulzer HK (2014) Factorial design as tool in chitosan nanoparticles development by ionic gelation technique. Colloids Surf A Physicochem Eng Asp 445:34–39

    Article  CAS  Google Scholar 

  63. Mitra T, Sailakshmi G, Gnanamani A, Mandal AB (2012) Preparation and characterization of malonic acid cross-linked chitosan and collagen 3D scaffolds: an approach on non-covalent interactions. J Mater Sci Mater Med 23:1309–1321

    Article  CAS  Google Scholar 

  64. Cervera MF, Heinämäki J, de la Paz N, López O, Maunu SL, Virtanen T, Hatanpää T, Antikainen O, Nogueira A, Fundora J, Yliruusi J (2011) Effects of spray drying on physicochemical properties of chitosan acid salts. AAPS PharmSciTech 12:637–649

    Article  CAS  Google Scholar 

  65. Huang H, Liu F, Chen S, Zhao Q, Liao B, Long Y, Zeng Y, Xia X (2013) Enhanced fluorescence of chitosan based on size change of micelles and application to directly selective detecting Fe3+ in humanserum. Biosens Bioelectron 42:539–544

    Article  CAS  Google Scholar 

  66. Tallury P, Kar S, Bamrungsap S, Huang Y-F, Tan W, Santra S (2009) Ultra-small water-dispersible fluorescent chitosan nanoparticles: synthesis, characterization and specific targeting. Chem Commun:2347–2349

    Google Scholar 

  67. Cheng M, Huang Y, Zhou H-j, Liu Z, Li J-f (2010) Rapid preparation and characterization of chitosan nanoparticles for oligonucleotide. Cur Appl Phys 10:797–800

    Article  Google Scholar 

  68. Kim D-G, Jeong Y-I, Choi C, Roh S-H, Kang S-K, Jang M-K, Nah J-W (2006) Retinol-encapsulated low molecular water-soluble chitosan nanoparticles. Int J Pharm 319:130–138

    Article  CAS  Google Scholar 

  69. Grenha A, Seijo B, Serra C, Remuñan-López C (2007) Chitosan nanoparticle-loaded mannitol microspheres: structure and surface characterization. Biomacromolecules 8:2072–2079

    Article  CAS  Google Scholar 

  70. Huang H-Y, Shieh Y-T, Shih C-M, Twu Y-K (2010) Magnetic chitosan/iron (II, III) oxide nanoparticles prepared by spray-drying. Carbohydr Polym 81:906–910

    Article  CAS  Google Scholar 

  71. Tozaki H, Odoriba T, Okada N, Fujita T, Terabe A, Suzuki T, Okabe S, Muranishi S, Yamamoto A (2002) Chitosan capsules for colon-specific drug delivery: enhanced localization of 5-aminosalicylic acid in the large intestine accelerates healing of TNBS-induced colitis in rats. J Controll Release 82:51–61

    Article  CAS  Google Scholar 

  72. Wilson B, Samanta MK, Santhi K, Kumar KPS, Ramasamy M, Suresh B (2010) Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine. Nanomedicine 6:144–152

    Article  CAS  Google Scholar 

  73. Varshosaz J, Jaffarian Dehkordi A, Golafshan S (2006) Colon-specific delivery of mesalazine chitosan microspheres. J Microencapsul 23:329–339

    Article  CAS  Google Scholar 

  74. Lorenzo-Lamosa ML, Remuñán-López C, Vila-Jato JL, Alonso MJ (1998) Design of microencapsulated chitosan microspheres for colonic drug delivery. J Controll Release 52:109–118

    Article  CAS  Google Scholar 

Download references

Acknowledgment

The author is thankful to Professor Swadesh mukul Santra of NanoScience Technology Center of the University of Central Florida for motivating me to this research. She is also thankful to the Principal of Asutosh college, Kolkata for academic support.

Important Web References Related to Drug Encapsulation and Delivery by Chitosan Nanoparticles

  1. (i)

    https://www.mdpi.com/1999-4923/9/4/53

  2. (ii)

    https://www.jstage.jst.go.jp/article/cpb/58/11/58_11_1423/_article/-char/ja/

  3. (iii)

    https://iopscience.iop.org/article/10.1088/0957-4484/18/40/405102/meta

  4. (iv)

    https://www.sciencedirect.com/science/article/abs/pii/S016836590100342X

  5. (v)

    https://www.sciencedirect.com/science/article/abs/pii/S0268005X16308700

Author information

Authors and Affiliations

  1. Department of Chemistry, Asutosh College under Calcutta University, Kolkata, India

    Srijita Basumallick

Authors
  1. Srijita Basumallick
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Singapore Pte Ltd.

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Basumallick, S. (2022). Synthesis of Biocompatible Chitosan Nanoparticles by Some Greener Methods for Drug Encapsulations. In: Handbook of Consumer Nanoproducts. Springer, Singapore. https://doi.org/10.1007/978-981-16-8698-6_49

Download citation

Publish with us

Policies and ethics

Search

Navigation